Much of the spotlight for coronavirus disease 2019 (COVID-19) is on the acute symptoms and recovery. However, many recovered patients face persistent physical, cognitive, and psychological symptoms well past the acute phase. Of these symptoms, fatigue is one of the most persistent and debilitating. In this “perspective article,” we define fatigue as the decrease in physical and/or mental performance that results from changes in central, psychological, and/or peripheral factors due to the COVID-19 disease and propose a model to explain potential factors contributing to post-COVID-19 fatigue. According to our model, fatigue is dependent on conditional and physiological factors. Conditional dependency comprises the task, environment, and physical and mental capacity of individuals, while physiological factors include central, psychological, and peripheral aspects. This model provides a framework for clinicians and researchers. However, future research is needed to validate our proposed model and elucidate all mechanisms of fatigue due to COVID-19.

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People with Parkinson’s disease (PwPD) often experience gait and balance problems that substantially impact their quality of life. Pharmacological, surgical, and rehabilitative treatments have limited effectiveness and many PwPD continue to experience gait and balance impairment. Transcranial direct current stimulation (tDCS) may represent a viable therapeutic adjunct. The effects of lower intensity tDCS (2 mA) over frontal brain areas, in unilateral and bilateral montages, has previously been explored; however, the effects of lower and higher intensity cerebellar tDCS (2 mA and 4 mA, respectively) on gait and balance has not been investigated. Seven PwPD underwent five cerebellar tDCS conditions (sham, unilateral 2 mA, bilateral 2 mA, unilateral 4 mA, and bilateral 4 mA) for 20 min. After a 10 min rest, gait and balance were tested. The results indicated that the bilateral 4 mA cerebellar tDCS condition had a significantly higher Berg Balance Scale score compared to sham. This study provides preliminary evidence that a single session of tDCS over the cerebellum, using a bilateral configuration at a higher intensity (4 mA), significantly improved balance performance. This intensity and cerebellar configuration warrants future investigation in larger samples and over repeated sessions.

Transcranial direct current stimulation (tDCS) is a form of non-invasive neuromodulation that is increasingly being utilized to examine and modify several cognitive and motor functions. Although tDCS holds great potential, it is difficult to determine optimal treatment procedures to accommodate configurations, the complex shapes, and dramatic conductivity differences among various tissues. Furthermore, recent demonstrations showed that up to 75% of the tDCS current applied to rodents and human cadavers was shunted by the scalp, subcutaneous tissue, and muscle, bringing the effects of tDCS on the cortex into question. Consequently, it is essential to combine tDCS with human neuroimaging to complement animal and cadaver studies and clarify if and how tDCS can affect neural function. One viable approach is positron emission tomography (PET) imaging. PET has unique potential for examining the effects of tDCS within the central nervous system in vivo, including cerebral metabolism, neuroreceptor occupancy, and neurotransmitter activity/binding. The focus of this review is the emerging role of PET and potential PET radiotracers for studying tDCS-induced functional changes in the human brain.

Transcranial direct current stimulation (tDCS) has previously shown different cortical excitability and neuropsychological effects between women and men. However, the sex-specific effects of tDCS on leg muscle fatigability has not been investigated. The purpose of this study was to determine the effects of a single session of 2 mA and 4 mA primary motor cortex tDCS on leg muscle fatigability in healthy young men and women in a crossover design. Twenty participants (women = 10) completed isokinetic fatigue testing (40 maximal reps, 120°/s) of the knee extensors and flexors in conjunction with sham, 2 mA, and 4 mA tDCS in a double-blind, randomized design. The fatigue index from each condition was calculated. Women had significantly greater knee extensor fatigability in the 4 mA condition compared to men (57.8 ± 6.8% versus 44.1 ± 18.4%; p = 0.041, d = 0.99). This study provides additional evidence that responses to tDCS may be sex-specific and highlights the necessity of accounting and powering for sex differences in future investigations.

Transcranial direct current stimulation (tDCS) has been shown to alter cortical excitability. However, it is increasingly accepted that tDCS has high inter- and intra-subject response variability, which currently limits broad application and has prompted some to doubt if the current can reach the brain. This study reports individual cerebral blood flow responses in people with multiple sclerosis and neurologically healthy subjects that experienced 5 min of anodal tDCS at 1 mA, 2 mA, 3 mA, and 4 mA over either the dorsolateral prefrontal cortex (DLPFC) or the primary motor cortex (M1). The most notable results indicated anticipated changes in regional cerebral blood flow (rCBF) in two regions of one DLPFC subject (2 mA condition), and expected changes in one M1 subject in the 2 mA and 4 mA conditions and in another M1 subject in the 2 mA condition. There were also changes contrary to the expected direction in one DLPFC subject and in two M1 subjects. These data suggest the effects of tDCS might be site-specific and highlight the high variability and individualized responses increasingly reported in tDCS literature. Future studies should use longer stimulation durations and image at various time points after stimulation cessation when exploring the effects of tDCS on cerebral blood flow (CBF).

Studies investigating the effects of transcranial direct current stimulation (tDCS) on fatigue and muscle activity have elicited measurable improvements using stimulation intensities ≤2 mA and submaximal effort tasks. The purpose of this study was to determine the effects of 2 mA and 4 mA anodal tDCS over the primary motor cortex (M1) on performance fatigability and electromyographic (EMG) activity of the leg muscles during a maximal isokinetic task in healthy young adults. A double-blind, randomized, sham-controlled crossover study design was applied. Twenty-seven active young adults completed four sessions, each spaced by 5-8 days. During session 1, dominance was verified with isokinetic strength testing, and subjects were familiarized with the fatigue task (FT). The FT protocol included 40 continuous maximum isokinetic contractions of the knee extensors and flexors (120 • /s, concentric/concentric). During Sessions 2-4, tDCS was applied for 20 min with one of three randomly assigned intensities (sham, 2 mA or 4 mA) and the FT was repeated. The anode and cathode of the tDCS device were placed over C3 and the contralateral supraorbital area, respectively. A wireless EMG system collected muscle activity during the FT. The 2 mA tDCS condition had significantly less torque (65.9 ± 32.7 Nm) during the FT than both the sham (68.4 ± 33.9 Nm, p < 0.001) and 4 mA conditions (68.4 ± 33.9 Nm, p = 0.001). Furthermore, the 2 mA condition (33.8 ± 11.7%) had significantly less EMG activity during the FT than both the sham (39.7 ± 10.6%, p < 0.001) and 4 mA conditions (40.5 ± 13.4%, p = 0.001). Contrary to previous submaximal isometric fatigue investigations, the 2 mA tDCS condition significantly reduced torque production and EMG activity of the leg extensors during a maximal isokinetic FT compared with the sham and 4 mA conditions. Also, torque production and EMG activity in the 4 mA condition were not significantly different from sham. Thus, the effects of tDCS, and the underlying mechanisms, might not be the same for different tasks and warrants more investigation.

Cannabis is one of the most common drugs in the United States and is the third most prevalent substance consumed by adults aged 50 years and older. Normal aging is associated with physiological changes that make older adults vulnerable to impaired function and geriatric conditions (e.g., falls, cognitive impairment). However, the impact of medical cannabis use on fall risk in older adults remains unexplored. The purpose of this study was to investigate if cannabis use in older adults influences fall risk, cognitive function, and motor function. It was hypothesized that older chronic cannabis users would perform worse than non-users on gait, balance, and cognitive tests. Sixteen older adults, split into cannabis Users and age- and sex-matched Non-Users groups (n = 8/group), participated in the study. The results indicate a higher fall risk, worse one leg standing balance performance, and slower gait speed in Users vs. Non-Users. No significant differences in cognitive function were found. Thus, chronic cannabis use was purported to exacerbate the poorer balance control and slower gait velocity associated with normal aging. Future mechanistic (e.g., neuroimaging) investigations of the short- and long-term effects of using a variety of cannabis products (e.g., THC/CBD ratios, routes of administration) on cognitive function, motor function, and fall incidence in older adults are suggested.